Controlled Release of Retinol in Cationic Co-Polymeric Nanoparticles for Topical Application (original) (raw)
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Encapsulation and controlled release of retinol from silicone particles for topical delivery
Retinol, a derivative of vitamin A, is a ubiquitous compound used to treat acne, reduce wrinkles and protect against conditions like psoriasis and ichthyosis. While retinol is used as the primary active ingredient (AI) in many skin care formulations, its efficacy is often limited by an extreme sensitivity to degrade and toxicity at high concentrations. While microencapsulation is an appealing method to help overcome these issues, few micro-encapsulation strategies have made a major translational impact due to challenges with complexity, cost, limited protection of the AI and poor control of the release of the AI. We have developed a class of silicone particles that addresses these challenges for the encapsulation, protection and controlled release of retinol and other hydro-phobic compounds. The particles are prepared by the sol-gel polymerization of silane monomers, which enables their rapid and facile synthesis at scale while maintaining a narrow size distribution (i.e., CV < 20%). We show that our particles can: (i) encapsulate retinol with high efficiency (> 85%), (ii) protect retinol from degradation (yielding a half-life 9× greater than unencapsulated retinol) and (iii) slowly release retinol over several hours (at rates from 0.14 to 0.67 μg cm −2 s −1/2). To demonstrate that the controlled release of retinol from the particles can reduce irritation, we performed a double blind study on human subjects and found that formulations containing our particles were 12–23% less irritating than identical formulations containing Microsponge® particles (an industry standard by Amcol, Inc.). To show that the silicone particles can elicit a favorable biological response, similar to the Microsponge® particles, we applied both formulations to reconstructed human epidermal tissues and found an upregulation of keratin 19 (K19) and a downregulation of K10, indicating that the reduced irritation observed in the human study was not caused by reduced activity. We also found a decrease in the production of interleukin-1α (IL-1α) compared to formulations containing the Microsponge particles, suggesting lower irritation levels and supporting the findings from the human study. Finally, we show that the silicone particles can encapsulate other AIs, including betamethasone, N, N-diethyl-meta-toluamide (DEET), homosalate and ingenol mebutate, establishing these particles as a true platform technology.
International journal of pharmaceutics, 2004
Poly(epsilon-caprolactone)/poly(ethylene glycol) (abbreviated as CE) diblock copolymers were synthesized to make core-shell type nanoparticles for all-trans-retinoic acid (atRA). Fluorescence spectroscopy showed that critical association concentration (CAC) value decreased at higher MW of CE diblock copolymer. Drug loading characteristics were studied under various experimental conditions. Drug contents and loading efficiency increased as the MW of poly(epsilon-caprolactone) (PCL) block of CE and initial drug feeding amount increased. Solvent used and preparation method also affected drug contents and loading efficiency. According to 1H NMR using CDCl3 and D2O, specific peaks of the PCL block and drug appearing in CDCl3, disappeared at D2O, suggesting hydrophobic core with hydrophilic shell formed in water. atRA release was faster at smaller MW of copolymer and lower drug contents. Nanoparticles prepared in DMF showed faster release rate compared with those prepared in THF or aceton...
BioMed Research International, 2021
Cationic nanocapsules represent a promising approach for topical delivery purposes. We elaborated on a novel formulation based on the cationic nanocapsules to enhance the pharmacodynamic efficacy, user compliance, and photostability of tretinoin (TTN). To achieve this goal, TTN nanocapsules were prepared by the nanoprecipitation method. In order to statistically optimize formulation variables, a Box-Behnken design, using Design-Expert software, was employed. Three independent variables were evaluated: total weight of the cationic acrylic polymer (X1), oil volume (X2), and TTN amount (X3). The particle size and encapsulation efficiency percent (EE%) were selected as dependent variables. The optimal formulation demonstrated spherical morphology under scanning electron microscopy (SEM), optimum particle size of 116.3 nm, and high EE% of 83.2%. TTN-loaded nanocapsules improved photostability compared to its methanolic solution. The in vitro release study data showed that tretinoin was r...
Materials Today Communications, 2020
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Proretinal nanoparticles: stability, release, efficacy, and irritation
International Journal of Nanomedicine, 2016
Despite many potent biological activities, retinoids such as retinoic acid (RA) and retinal possess dose-related broad side effects. In this study, we show that this problem, which has been unsolvable for a long time, can be tackled through a controlled release strategy in which retinal is continuously delivered to the skin via sustained release from proretinal nanoparticles. The water dispersible proretinal nanoparticles are stable when kept in water at neutral pH and at room temperature for 8 months under light-proof conditions, and show sustained release of retinal into human synthetic sebum at a pH of 5. In the daily topical application tests performed for 4 weeks on rats' skin, the nanoparticles showed superior ability to increase epidermal thickness compared to RA and retinal, with no skin irritation observed for the proretinal particles, but severe skin irritation observed for RA and free retinal. When tested under occlusion conditions in human volunteers, insignificant skin irritation was observed for the proretinal nanoparticles. The 12-week, double-blind, split-face study on human volunteers indicates better antiaging efficacy of the particles as compared to the free RA.
Retinoids: new use by innovative drug-delivery systems
Expert Opinion on Drug Delivery, 2009
Background: Retinoids represent an old class of bioactives used in the treatment of different skin pathologies (such as acne and psoriasis) and in the treatment of many tumors. Unfortunately, they present several side effects, i.e., burning of skin and general malaise after systemic administration and they are very unstable after exposition to light. Methods: One of the most promising new approaches for reducing the side effects of retinoids while improving their pharmacological effect is the use of drug-delivery devices. This review explains the current status of retinoid drug transport, which has been developing over the last few years, explaining the modification of their biopharmaceutical properties in detail after encapsulation/inclusion in vesicular and polymeric systems. Results/conclusion: Different colloidal and micellar systems containing retinoid drugs have been realized furnishing important potential advancements in traditional therapy.
2008
Skin, hair and mucosal surfaces are useful targets for the delivery of active compounds, botanicals and, importantly, drugs. Encapsulation provides an invaluable tool to the cosmetic and/or pharmaceutical formulator, providing great flexibility in the choice of delivery mechanisms and excipients that can be used. Dispersions of solid lipid nanoparticles (SLNs) were prepared using biodegradable materials generally regarded as safe by a melt-emulsify-chill (MEC) method. Among the materials encapsulated in SLNs were hydrophobic active pharmaceutical ingredients, antiviral and fungicidal compounds, organic UV absorbers and fluorescent dyes. The loading, adhesion and intracellular localization of the SLNs were studied as a function of surface charge. The MEC process can easily, and cheaply, produce a range of solid lipid nanoparticles (SLNs) “smart colloids” that offer flexibility in formulation, increased efficacy and decreased formulation complexity. The method is general and can be ap...
DESIGN & EVALUATION OF NOVEL RETINOL- ENCAPSULATED CHITOSAN NANOPARTICLES
The aim of this study was to encapsulate retinol into chitosan nanoparticles and reconstitute it into aqueous solution. Retinol-encapsulated chitosan nanoparticles were prepared for application of cosmetic and pharmaceutical applications. Retinol-encapsulated chitosan nanoparticle has a spherical shape and its particle sizes were around 50–200 nm according to the drug contents. Particle size was increased according to the increase of drug contents. Solubility of retinol is able to increase by encapsulation into chitosan nanoparticles more than 1600-fold. It was suggested that retinol was encapsulated into chitosan nanoparticles by ion complex as a result of FT-IR spectra. Specific peak of chitosan at 1590 cm −1 was divided to semi-doublet due to the electrostatic interaction between amine group of chitosan and hydroxyl group of retinol. At 1 H NMR spectra, specific peaks of retinol disappeared when retinol-encapsulated chitosan nanoparticles were reconstituted into D 2 O while specific peaks both of retinol and chitosan appeared at D 2 O/DMSO (1/4, v/v) mixture. XRD patterns also showed that crystal peaks of retinol were disappeared by encapsulation into chitosan nanoparticles. Retinol-encapsulated nanoparticles were completely reconstituted into aqueous solution as same as original aqueous solution and zeta potential of reconstituted chitosan nanoparticles was similar to their original solution. At HPLC study, retinol was stably and efficiently encapsulated into chitosan nanoparticles.
Drug–polymer interaction in the all-trans retinoic acid release from chitosan microparticles
Journal of Thermal Analysis and Calorimetry, 2007
Chitosan microparticles were prepared with the purpose of incorporating all-trans retinoic acid (ATRA). Morphology, drug content, release behavior and the interaction between chitosan and ATRA were investigated. Chitosan microparticles presented irregular and rough surface and drug content of 47±3%. The results of DSC and IR spectroscopy demonstrated interaction between drug and polymer resulting from retinoate or retinoamide formation. The drug release study showed that approximately 90% of drug was not released from microparticles until the end of experiment (48 h). That release behavior was probably due to the strong drug-polymer interaction and the more compact network of microparticles formed.
International journal of pharmaceutics, 2004
To prepare a self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate, with enhanced dissolution and better chance of oral absorption. All-trans-retinol acetate SNEDDS was prepared using different concentrations of soybean oil (solvent) Cremophor EL (surfactant) and Capmul MCM-C8 (co-surfactant). Particle size and turbidity of the SNEDDS were determined after adding water to the oily solution. Dissolution profile of SNEDDS filled in hydroxyl propyl methyl cellulose (HPMC) capsules was determined by using water in USP apparatus 2. Ternary phase diagrams were constructed to identify the self-nanoemulsified region. The SNEDDS were evaluated by the visual observation, turbidity in nephrometric turbidity units (NTU), mean particle size (microm) and Fourier transformed-infrared spectroscopy (FT-IR). SNEDDS were thermally characterized using differential scanning calorimetry (DSC) to ensure the compatibility of the SNEDDS ingredient. From the data obtained in this wor...